Objective—To develop an IM xenograft model of canine osteosarcoma in mice for the purpose of evaluating effects of radiation therapy on tumors.
Animals—27 athymic nude mice.
Procedures—Mice were randomly assigned to 1 of 3 groups of 9 mice each: no treatment (control group), radiation at 10 Gy, or radiation at 15 Gy. Each mouse received 5 × 105 highly metastasizing parent osteosarcoma cells injected into the left gastrocnemius muscle. Maximum tumor diameter was determined with a metric circles template to generate a tumor growth curve. Conscious mice were restrained in customized plastic jigs allowing local tumor irradiation. The behavior and development of the tumor xenograft were assessed via evaluations of the interval required for tumor-bearing limbs to reach diameters of 8 and 13 mm, extent of tumor vasculature, histomorphology of tumors, degree of tumor necrosis, and existence of pulmonary metastasis and clinical disease in affected mice.
Results—Tumor-bearing limbs grew to a diameter of 8 mm (0.2-g tumor mass) in a mean ± SEM interval of 7.0 ± 0.2 days in all mice. Interval to grow from 8 to 13 mm was significantly prolonged for both radiation therapy groups, compared with that of the control group. Histologic evaluation revealed the induced tumors were highly vascular and had characteristics consistent with those of osteosarcoma. Pulmonary metastasis was not detected, and there was no significant difference in percentage of tumor necrosis between groups.
Conclusions and Clinical Relevance—A reliable, repeatable, and easily produced IM xenograft model was developed for in vivo assessment of canine osteosarcoma.
Objective—To characterize the radiosensitivity and capacity for sublethal damage repair (SLDR) of radiation-induced injury in 4 canine osteosarcoma cell lines.
Sample Population—4 canine osteosarcoma cell lines (HMPOS, POS, COS 31, and D17).
Procedures—A clonogenic colony-forming assay was used to evaluate the cell lines' intrinsic radiosensitivities and SLDR capacities. Dose-response curves for the cell lines were generated by fitting the surviving fractions after radiation doses of 0 (control cells), 1, 2, 3, 6, and 9 Gy to a linear quadratic model. To evaluate SLDR, cell lines were exposed to 2 doses of 3 Gy (split-dose experiments) at an interval of 0 (single 6-Gy dose), 2, 4, 6, or 24 hours, after which the surviving fractions were assessed.
Results—Mean surviving fraction did not differ significantly among the 4 cell lines at the radiation doses tested. Mean surviving fraction at 2 Gy was high (0.62), and the α/β ratios (predictor of tissue sensitivity to radiation therapy) for the cell lines were low (mean ratio, 3.47). The split-dose experiments revealed a 2.8- to 3.9-fold increase in cell survival when the radiation doses were applied at an interval of 24 hours, compared with cell survival after radiation doses were applied consecutively (0-hour interval).
Conclusions and Clinical Relevance—Results indicated that these canine osteosarcoma cell lines are fairly radioresistant; α/β ratios were similar to those of nonneoplastic, lateresponding tissues. Future clinical investigations should involve increasing the fraction size in a manner that maximizes tumor killing without adverse effects on the nonneoplastic surrounding tissues.
Objective—To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice.
Animals—27 athymic nude mice.
Procedures—To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated.
Results—Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group.
Conclusions and Clinical Relevance—Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs.
Impact for Human Medicine—Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.
Objective—To compare heartworm serum antibody
(Ab) and antigen (Ag) test results, using commercial
laboratories and in-house heartworm test kits, with
necropsy findings in a population of shelter cats.
Animals—330 cats at an animal shelter.
Procedure—Between March and June 1998, 30 ml
of blood was collected from the cranial and caudal
venae cavae of 330 cats that were euthanatized at a
local animal shelter. Results of heartworm Ab and
Ag serologic tests for heartworm infection were
compared with necropsy findings in this population
of cats, using commercial laboratories and in-house
test kits to measure serum Ab and Ag concentrations.
Results—On necropsy, adult Dirofilaria immitis were
found in 19 of 330 (5.8%) cats. Combining results
from serum Ab and Ag tests achieved higher sensitivities
than using serum Ab and Ag test results alone
(ie, maximum sensitivities of 100% vs 89.5%, respectively),
whereas use of serum Ag and Ab test results
alone achieved higher specificities compared with the
use of a combination of serum Ab and Ag results (ie,
maximum specificities of 99.4% vs 92.9%, respectively).
Conclusions and Clinical Relevance—On the basis
of our findings, if a cat has clinical signs that suggest
heartworm disease despite a negative heartworm
serum Ab test result, an alternative heartworm Ab
test, a heartworm Ag test, thoracic radiography, or
two-dimensional echocardiography should be performed.
(J Am Vet Med Assoc 2000;216:693–700)